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Bialellic Mutations in Tetratricopeptide Repeat Domain 7A (TTC7A) Cause Common Variable Immunodeficiency-Like Phenotype with Enteropathy

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Correspondence to Sinisa Savic.

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Capsule Summary

TTC7A deficiency typically causes severe gastrointestinal manifestations such as multiple intestinal atresia or early-onset inflammatory bowel disease. In some cases, this is associated with severe combined immunodeficiency. Partial loss-of-function mutations appear to be associated with a milder phenotype resulting in common variable immunodeficiency-like condition with enteropathy.

Electronic supplementary material

Fig E1

Sanger sequence electropherogram of pedigree. Sanger sequence electropherogram of the proband II.ii for exon 16/20 c.1817 aAg/aGg (K606R) and exon 17/20 c.2014 Tct/Cct (S672P). Heterozygosity of A1817G paternally I.i and T2014C maternally I.ii. Healthy siblings II.i, II.iii and II.iv (arranged by age left to right on pedigree) show no presence of affected alleles. (GIF 71 kb)

High resolution image (TIFF 25622 kb)

Fig E2

Ribbon structure model of TTC7A and tetratricopeptide repeat domains. All known pathogenic variants in apoptotic enterocolitis, multiple intestinal atresias, combined immunodeficiency, and enteropathy-lymphocytopenia-alopecia are mapped. Annotation colors match that of the gene representation of Fig. 1 A. Protein changes, purple; stop codon, red; frame shift, green; exon skipping causing variants, orange; retained intron, blue. Tetratricopeptide repeat domains (TPR) are identified as cartoons also corresponding to horizontal bars shown in Fig. 1 A. Tetratricopeptide repeat domains (1–9) 121–157 and 177–210 Red, 414–447 orange, 497–531 yellow, 533–565 Green, 566–599 Cyan, 745–778 Blue, 780–812 Purple, 813–846 Magenta. (GIF 215 kb)

High resolution image (TIFF 6622 kb)

Fig E3

Modeling report. Detailed template report for data used with Phyre2 software indicating alignment, coverage, confidence and % i.d. Template Information 1–20 used for model construction. (PDF 858 kb)

Fig E4

Sequence structure report. Phyre2 software report of secondary structure and disorder prediction showing disorder confidence and conserved domain information. (PDF 172 kb)

Table E1

(DOCX 41 kb)

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Lawless, D., Mistry, A., Wood, P.M. et al. Bialellic Mutations in Tetratricopeptide Repeat Domain 7A (TTC7A) Cause Common Variable Immunodeficiency-Like Phenotype with Enteropathy. J Clin Immunol 37, 617–622 (2017).

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